The proposed research will deal with biological aspects of iron chelates capable of reversible oxygen binding, both (a) synthetic and (b) the naturally occurring hemoglobin (stroma-free) and some of its modifications. The synthetic chelates, to be made by Dr. Baldwin of MIT as part of a collaborative program, will be of the "capped" and "strapped" porphyrin types, each capable of preventing irreversible oxidation of the iron. They will be obtained in forms suitable for biological use. Sulfonation of these compounds has been found effective to give water solubility and protein-binding capability, when these properties are desired. The modified hemoglobins will be (a) complexes between hemoglobin and such compounds as Dextran, hydroxyethyl starch, and high molecular weight polyols, in order to increase circulatory dwell time over that of free hemoglobin and (b) additional products with organic phosphate such as pyridoxal phosphate to offset possible shifts of the O2-Hb dissociation curve. All of the compounds will be administered singly to animals and will also be incorporated into artificial blood substitutes to be used for partial and total blood replacement. The latter will be carried out by the method demonstrated to give healthy surviving rats with hemoglobin perfusion, total perfusion followed by 24-48 hours slow infusion. The fate of the compounds in vivo and the extent to which the intact chelate is eliminated will be determined. The pO2, pCO2, pH, oxygen content, pyruvate and lactate concentrations of the circulating fluid will be measured. Blood cell and protein analyses, blood volume and other related determinations will be carried out. All compounds will be studied in organ perfusion and tested for toxicity in tissue culture.